Chemical carcinogens ingested in the diet either as common food constituents or food additives or contaminants, are believed to play a major etiological role in the increasing incidence of carcinoma of the colon in the developed countries. Many of these potential carcinogens undergo biotransformation (inactivation) at the site of their entry in the body or in the liver. Most of these inactivation reactions are catalyzed by microsomal mixed function oxidase systems of which cytochrome P-450 and cytochrome P-450 reductase are essential components. Whereas the nature, function and regulation of these oxidizing enzyme systems in the liver, and more recently in the small intestine, have been elucidated, little is known about the metabolism, biotransformation and potential inactivation of ingested carcinogens and the role of possible cocarcinogens in the colonic mucosa, except that mixed function oxidase activity has been identified in this tissue. The proposed project is designed to investigate the nature and activity and regulation of mixed function oxidases and of their component cytochrome P-450 in the colonic mucosa of rats under a variety of experimental and nutritional conditions. Particular attention will be paid to evolving changes in the function and activities during chemically-induced carcinogenesis. In analogy with previous findings in the small intestine, cytochrome P-450 and mixed function oxidase activity will be studied primarily in the most mature cell populations of the mucosal surface, where these enzymes are expected to elucidate the role of biotransformation mechanisms in the colonic mucosa in the production or prevention of cancer of the colon.